P793: EFFICACY AND IN VIVO EFFECTS OF PORCINE ANTIHUMAN LYMPHOCYTE IMMUNOGLOBULIN COMPARED TO RABBIT ANTITHYMOCYTE IMMUNOGLOBULIN IN SEVERE APLASTIC ANEMIA
Authors: Guangsheng He, Yu Sun, Yingying Zhang, Chuan He, Xuemei Wu
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: In China, the only two ATGs currently available for immunosuppressive therapy (IST) of severe aplastic anemia (SAA) are porcine antihuman lymphocyte immunoglobulin (pATG) and rabbit antithymocyte immunoglobulin (rATG). Several retrospective studies of the differences in efficacy between pATG and rATG have been reported, but these studies are limited in scope. Aims: To compare the hematologic responses and to investigate the mechanisms in patients with SAA treated with pATG or rATG based immunosuppressive therapy. The patients were intravenously treated with either pATG 30 mg/kg/d or rATG 3.5 mg/kg/d for five consecutive days. Methods: We conducted a prospective, non-randomized, controlled clinical trial enrolling a total of 56 patients with SAA (38 in the pATG group vs 18 in the rATG group). Oral CsA was started from day six, 3–5 mg/kg/d for adults, and 5 mg/kg/d for children, 2 to 3 times per day, 1 mg/kg Bid for those who could not take it orally and maintained for more than 3 hours each time. Treatments such as androgen, hematopoietic growth factors, and supportive therapies did not differ between the groups. Results: In comparison to the rATG group (33.3%), the pATG group displayed a significantly higher hematologic response rate at three months (68.4%, P = 0.013). The pATG group also showed a higher six-month hematologic response rate than the rATG group (65.8% vs 50.0%), though the difference was not statistically significant (P = 0.259). The three-month OR rates for patients ≥ 18 years and for patients with SAA were significantly higher in the pATG group than in the rATG group. The infection rate in the first month after treatment was lower in the pATG group than in the rATG group(36.8 vs 61.1%), though the difference was not statistically significant (P = 0.088). The pATG and rATG groups had two and four early deaths, respectively, with premature mortality rates of 5.3% and 22.2% (P = 0.077). 87.5% of all deaths were directly caused by infection. Both ATGs resulted in the depletion of peripheral blood lymphocytes after treatment. The rATG group showed more severe depletion and slower recovery of CD4+ and CD8+ T cells. The depletion of CD4+ T cells caused by pATG/rATG lasted longer than CD8+ T cells. In addition, elevated proportions and counts of regulatory T cells (Treg, defined as CD4+CD25+CD127-) were observed in both pATG and rATG groups after infusion. We used low cytometry to test whether ATG in the patient’s plasma could combine with normal human peripheral blood lymphocytes. The pATG showed more durable binding to lymphocytes. This is consistent with the in vivo pharmacokinetics of the two types of ATG that we studied. Summary/Conclusion: The pATG group had a higher three-month response rate and a similar six-month hematological response rate compared to the rATG group. In comparison with pATG, rATG had a stronger and longer lasting immunosuppressive effect. However, we did not observe a better efficacy in the rATG group. In our study, rATG resulted in more severe lymphocyte depletion and neutropenia, which might be the chief reason for the higher rate of infection and early mortality. This study is the first prospective clinical trial in China comparing in vivo effects and efficacy of pATG and rATG, which could be valuable for guiding the clinical application of these two drugs.Figure 1. Peripheral blood cell count changes in patients treated with different types of ATG (A) absolute lymphocyte count and (B) absolute neutrophil count. *P < 0.05; **P < 0.01; ***P < 0.001.Figure 2. Comparison of platelet counts between pATG and rATG groups.Figure 3. Changes in different lymphocyte populations after pATG or rATG treatment.Figure 4. Pharmacokinetics of the two types of ATG.Figure 5. pATG/rATG in patients’ plasma binding to normal human peripheral blood lymphocytes. Keywords: Immunosuppressive therapy, Antithymocyte globulin, Severe aplastic anemia